A traditional Chinese medicine composition for treating metabolic dysfunction-related fatty liver disease

Abstract

The application belongs to the technical field of traditional Chinese medicines, and discloses a traditional Chinese medicine composition for treating metabolic dysfunction related fatty liver disease, and the technical scheme is characterized by comprising the following raw medicinal materials in parts by weight: 5-15 parts of angelica sinensis, 10-20 parts of white atractylodes, 10-20 parts of red peony root, 10-20 parts of white peony root, 15-30 parts of poria cocos, 10-20 parts of alisma orientalis, 15-30 parts of salvia miltiorrhiza, 5-12 parts of curcuma zedoary, 10-20 parts of raw hawthorn, 5-15 parts of lotus leaf, 5-15 parts of dried tangerine or orange peel, and 3-10 parts of licorice root. The liver-regulating and phlegm-dissolving traditional Chinese medicine composition provided by the application is a safe and effective traditional Chinese medicine compound for treating MASLD, has certain curative effect on improving clinical symptoms such as chest and rib distension, lassitude and debilitation, dry mouth and dry throat, relieving liver load, and reducing the levels of TC and TG, and no obvious drug adverse reactions are found, so the application is worthy of clinical promotion and application.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and more specifically, to a traditional Chinese medicine composition for treating fatty liver disease associated with metabolic dysfunction. Background Technology

[0002] Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is one of the most common chronic liver diseases. Its development is closely related to components of metabolic syndrome such as obesity, type 2 diabetes, dyslipidemia, and hypertension. MASLD can progress to metabolic-associated steatohepatitis (MASH), liver fibrosis, cirrhosis, and even hepatocellular carcinoma, seriously threatening human health and imposing a heavy medical and economic burden.

[0003] Currently, Western medicine treatment for MASLD mainly revolves around lifestyle interventions (dietary control, exercise), lipid-lowering drugs (such as statins), insulin sensitizers (such as metformin and thiazolidinediones), and hepatoprotective and anti-inflammatory drugs (such as silymarin and vitamin E). However, existing treatments have significant shortcomings: while lifestyle interventions are the first-line recommendation, long-term patient adherence is poor, and relying solely on exercise and dietary adjustments is insufficient to achieve sustained weight loss and metabolic improvement; lipid-lowering drugs pose a potential risk of hepatotoxicity in patients with liver dysfunction, and the safety of high-dose long-term use of antioxidants such as vitamin E remains controversial. Therefore, developing safe, effective drugs with a clearly defined mechanism of action for the treatment of MASLD is of significant clinical importance.

[0004] Traditional Chinese medicine (TCM) has accumulated rich clinical experience in treating fatty liver, forming various treatment methods such as "strengthening the spleen and removing dampness, soothing the liver and regulating qi, promoting blood circulation and removing blood stasis, and resolving phlegm and unblocking the meridians." In recent years, numerous patents and clinical studies on TCM compound prescriptions have reported the potential advantages of TCM compositions in improving liver function, regulating lipid metabolism, and reducing hepatic fatty infiltration. In terms of TCM syndrome differentiation, phlegm-dampness obstruction syndrome is one of the common syndromes of fatty liver, characterized by spleen dysfunction, internal retention of dampness, accumulation of dampness into phlegm, and phlegm-dampness obstructing the meridians. For this syndrome type, some traditional Chinese medicine compound prescriptions (such as modified Wendan Decoction and modified Erchen Decoction) have been used in clinical practice, but the following problems are common: (1) Most compound prescriptions are based on classic prescriptions with additions and subtractions, and lack innovative prescriptions for liver and spleen disharmony, phlegm obstruction, and phlegm obstruction syndrome; (2) Existing studies are mostly based on clinical experience summaries or small sample case reports, and lack high-quality clinical data compared with lifestyle interventions; (3) Studies on the mechanism of action mostly stay at the level of traditional pharmacodynamics, and rarely systematically explain from the modern biological axis of "intestinal flora-short chain fatty acids-lipid metabolism".

[0005] Therefore, developing a traditional Chinese medicine composition that uses "regulating the liver and resolving turbidity" as its treatment principle, targets fatty liver with phlegm and turbidity obstruction, can produce synergistic effects with lifestyle interventions, and elucidates its mechanism of action from the perspective of gut microbiota, has important clinical value and innovative significance. Summary of the Invention

[0006] The present invention aims to provide a traditional Chinese medicine composition for treating fatty liver disease related to metabolic dysfunction, in order to solve the problem of the lack of optimized combination of specific formulas for fatty liver disease with phlegm-dampness obstruction in the prior art.

[0007] Specifically, the present invention is achieved through the following technical solutions:

[0008] In a first aspect, the present invention provides a traditional Chinese medicine composition for treating fatty liver disease associated with metabolic dysfunction, the traditional Chinese medicine composition comprising the following raw medicinal materials in parts by weight: Angelica sinensis 5-15 parts, Atractylodes macrocephala 10-20 parts, Paeonia lactiflora 10-20 parts, Paeonia veitchii 10-20 parts, Poria cocos 15-30 parts, Alisma plantago-aquatica 10-20 parts, Salvia miltiorrhiza 15-30 parts, Curcuma zedoaria 5-12 parts, Crataegus pinnatifida 10-20 parts, Nelumbo nucifera leaf 5-15 parts, Citrus reticulata peel 5-15 parts, and Glycyrrhiza uralensis 3-10 parts.

[0009] Preferably, the traditional Chinese medicine composition consists of the following raw medicinal materials in parts by weight: 10 parts Angelica sinensis, 15 parts Atractylodes macrocephala, 15 parts Paeonia lactiflora, 15 parts Paeonia veitchii, 20 parts Poria cocos, 15 parts Alisma plantago-aquatica, 20 parts Salvia miltiorrhiza, 9 parts Curcuma zedoaria, 15 parts Crataegus pinnatifida, 10 parts Nelumbo nucifera leaf, 10 parts Citrus reticulata peel, and 6 parts Glycyrrhiza uralensis.

[0010] Preferably, the traditional Chinese medicine composition has the effects of regulating liver function, resolving phlegm, and lowering lipids. It is used to treat fatty liver disease related to metabolic dysfunction, specifically those diagnosed by traditional Chinese medicine as phlegm-dampness obstruction syndrome. One dose is taken daily, decocted in water and taken orally in two divided doses.

[0011] In a second aspect, the present invention provides a method for preparing a drug for treating fatty liver disease related to metabolic dysfunction using the above-mentioned traditional Chinese medicine composition, comprising: weighing the raw materials in the traditional Chinese medicine composition by weight, pulverizing and / or decocting them, and adding or not adding medically acceptable excipients to prepare any acceptable drug.

[0012] Preferably, the mesh size of the pulverized material is 10 to 80 mesh.

[0013] Preferably, the ingredients need to be soaked for 30-60 minutes before frying.

[0014] Preferably, the decoction includes: adding 6 to 12 times the total weight of the raw materials to water and decocting for 30 to 90 minutes; after filtration, adding 4 to 8 times the total weight of the raw materials to water to decoct for 20 to 60 minutes.

[0015] Preferably, the dosage form of the drug is a decoction, powder, granules, tablets, or capsules.

[0016] Preferably, the excipient is one or more of dextrin, soluble starch, lactose, microcrystalline cellulose, mannitol, and magnesium stearate.

[0017] In a third aspect, the present invention provides a medicament for treating fatty liver disease associated with metabolic dysfunction prepared using the above method.

[0018] In a fourth aspect, the present invention provides the use of the above-mentioned drug in the preparation of a drug for treating fatty liver disease associated with metabolic dysfunction.

[0019] The formula analysis of the traditional Chinese medicine composition described in this invention is as follows:

[0020] Angelica sinensis: The dried root of Angelica sinensis (Oliv.) Diels, a plant in the Apiaceae family. Properties and Channels Entered: Sweet, pungent, warm. Enters the Liver, Heart, and Spleen channels. Functions and Indications: Nourishes and invigorates blood, regulates menstruation and relieves pain, moistens the intestines and promotes bowel movement. Used for blood deficiency and chlorosis, dizziness and palpitations, irregular menstruation, amenorrhea and dysmenorrhea, abdominal pain due to deficiency and cold, rheumatic arthralgia, traumatic injuries, carbuncles and sores, and constipation due to intestinal dryness. Angelica sinensis infused with wine invigorates blood and regulates menstruation. Used for amenorrhea and dysmenorrhea, rheumatic arthralgia, and traumatic injuries.

[0021] Atractylodes macrocephala: This product is the rhizome of Atractylodes macrocephala Koidz., a plant in the Asteraceae family. It is warm in nature and sweet and bitter in taste. It enters the spleen and stomach meridians. Its functions include strengthening the spleen, replenishing qi, drying dampness and promoting diuresis, stopping sweating, and calming the fetus. Indications: It strengthens the spleen and replenishes qi, dries dampness and promotes diuresis, stops sweating, and calms the fetus. It is used for spleen deficiency with poor appetite, abdominal distension and diarrhea, phlegm retention with dizziness and palpitations, edema, spontaneous sweating, and threatened abortion.

[0022] Red peony root: The dried root of Paeonia lactiflora Pall. or Paeonia veitchii Lynch, both belonging to the Ranunculaceae family. Properties and Channels Entered: Bitter, slightly cold. Enters the Liver channel. Functions and Indications: Clears heat and cools the blood, disperses blood stasis and relieves pain. Used for heat entering the blood level, febrile rashes, hematemesis, epistaxis, red and swollen eyes, hypochondriac pain due to liver stagnation, amenorrhea, dysmenorrhea, abdominal masses, traumatic injuries, carbuncles, and sores.

[0023] White peony root: The dried root of Paeonia lactiflora Pall., a plant in the Ranunculaceae family. Functions and indications: Bitter, sour, slightly cold. Enters the liver and spleen meridians. Functions and indications: Nourishes blood and regulates menstruation, astringes yin and stops sweating, softens the liver and relieves pain, calms liver yang. Used for blood deficiency and chlorosis, irregular menstruation, spontaneous sweating, night sweats, hypochondriac pain, abdominal pain, limb spasms, headache, and dizziness.

[0024] Poria cocos: The sclerotium of the fungus Poriacocos (Schw.) Wolf. (family Polyporaceae). It is neutral in nature and sweet and bland in taste. It enters the Heart, Lung, Spleen, and Kidney meridians. Functions and indications: It promotes diuresis and eliminates dampness, strengthens the spleen and calms the mind. It is used for edema with scanty urine, phlegm retention with dizziness and palpitations, spleen deficiency with poor appetite, loose stools and diarrhea, restlessness, palpitations, and insomnia.

[0025] Alisma plantago-aquatica (Sam.) Juzep. or Alisma plantago-aquatica Linn., belonging to the Alismataceae family, is a dried tuber. Its properties and channels are sweet, bland, and cold. It enters the Kidney and Bladder channels. Its functions and indications include promoting diuresis and eliminating dampness, clearing heat, resolving turbidity, and lowering lipids. It is used for dysuria, edema, diarrhea with scanty urine, phlegm retention and dizziness, painful urination due to heat, and hyperlipidemia.

[0026] Danshen: The root and rhizome of *Salvia miltiorrhiza* Bge., a plant in the Lamiaceae family. Properties and Channels Entered: Slightly cold in nature, bitter in taste. Enters the Heart and Liver channels. Functions and Indications: Removes blood stasis and relieves pain, invigorates blood circulation and alleviates dysmenorrhea, clears the heart and relieves irritability. Used for chest pain, abdominal and hypochondriac pain, abdominal masses, arthralgia due to heat, insomnia, irregular menstruation, dysmenorrhea, amenorrhea, and sores and swelling.

[0027] Curcuma zedoaria: The dried rhizome of Curcuma phaeocaulis Val., Curcuma wangsiensis S.G.Leeet C.F.Liang, or Curcuma wenyujin Y.H.Chenet C.Ling (all belonging to the ginger family). Properties and Channels Entered: Pungent, bitter, warm. Enters the Liver and Spleen channels. Functions and Indications: Promotes qi circulation and breaks up blood stasis, eliminates stagnation and relieves pain. Used for abdominal masses, amenorrhea due to blood stasis, chest pain, and abdominal distension due to food stagnation.

[0028] Raw hawthorn: The dried, ripe fruit of *Crataegus pinnatifida* Bge. var. major N.E.Br. or *Crataegus pinnatifida* Bge., belonging to the Rosaceae family. Properties and Channels Entered: Sour, sweet, slightly warm. Enters the spleen, stomach, and liver channels. Functions and Indications: Promotes digestion and strengthens the stomach, regulates qi and disperses blood stasis, clears turbidity and lowers lipids. Used for food stagnation, abdominal distension, diarrhea and abdominal pain, amenorrhea due to blood stasis, postpartum blood stasis, stabbing pain in the heart and abdomen, chest pain, hernia pain, and hyperlipidemia.

[0029] Lotus leaf: The dried leaf of *Nelumbonucifera Gaertn.*, a plant in the Nymphaeaceae family. Properties and Channels Entered: Bitter, neutral. Enters the Liver, Spleen, and Stomach channels. Functions and Indications: Clears summer heat and dampness, promotes the upward movement of clear Yang, cools the blood and stops bleeding. Used for summer heat and thirst, summer heat and dampness diarrhea, spleen deficiency diarrhea, blood heat causing vomiting and nosebleeds, hematochezia and metrorrhagia. Charred lotus leaf has astringent properties, resolves blood stasis, and stops bleeding. Used for hemorrhage and postpartum dizziness.

[0030] Dried tangerine peel: The dried, mature peel of Citrus reticulata Blanco and its cultivated varieties, belonging to the Rutaceae family. Properties and Channels Entered: Bitter, pungent, warm. Enters the Lung and Spleen channels. Functions and Indications: Regulates Qi and strengthens the Spleen, dries dampness and resolves phlegm. Used for abdominal distension, poor appetite, vomiting and diarrhea, and cough with excessive phlegm.

[0031] Licorice: The root and rhizome of *Glycyrrhiza uralensis* Fisch., *Glycyrrhiza inflata* Bat., or *Glycyrrhiza glabra* L., all belonging to the genus *Glycyrrhiza* of the legume family. Properties and Channels Entered: Sweet in taste, neutral in nature, entering the spleen, stomach, and lung channels. Functions and Indications: Tonifies the spleen and replenishes qi, clears heat and detoxifies, resolves phlegm and relieves cough, alleviates spasms and pain, and harmonizes other herbs. Used for spleen and stomach weakness, fatigue, palpitations, shortness of breath, cough with excessive phlegm, abdominal and limb spasms and pain, carbuncles and boils, and to alleviate the toxicity and harshness of other drugs.

[0032] This invention is based on the treatment principle of "regulating the liver and strengthening the spleen, removing blood stasis and resolving turbidity" and the syndrome of "internal obstruction of phlegm and turbidity." The formula uses Angelica sinensis, Paeonia lactiflora, and Paeonia veitchii to nourish blood, soften the liver, and promote blood circulation; Atractylodes macrocephala and Poria cocos to strengthen the spleen and eliminate dampness to prevent the generation of phlegm; Alisma plantago-aquatica, Crataegus pinnatifida, and Nelumbo nucifera to promote diuresis, resolve turbidity, lower lipids, and eliminate accumulation; Salvia miltiorrhiza and Curcuma zedoaria to promote blood circulation, remove blood stasis, and resolve stagnation; Citrus reticulata peel to regulate qi, strengthen the spleen, dry dampness, and resolve phlegm; and Glycyrrhiza uralensis to harmonize the other herbs. The entire formula works synergistically to regulate the liver and qi, resolve phlegm and turbidity, and promote blood circulation and unblock the meridians, embodying the principle of "simultaneous regulation of the liver and spleen, and simultaneous treatment of phlegm and blood stasis." It supplements and innovates upon the existing compound formulas for fatty liver that primarily focus on "strengthening the spleen."

[0033] Compared with the prior art, the present invention has the following advantages:

[0034] 1. This invention is based on Traditional Chinese Medicine (TCM) theory and uses traditional Chinese herbal formulas, embodying the characteristics of TCM's "holistic view" and "syndrome differentiation and treatment," and aligning with the national policy of vigorously developing TCM and promoting its inheritance and innovation. The widespread application of this invention will help enhance the influence and recognition of TCM in the prevention and treatment of metabolic diseases. Through early intervention and improvement of metabolic disorders, this invention is expected to delay or prevent disease progression, reduce the incidence of end-stage liver disease, thereby improving patients' quality of life and reducing long-term medical expenses.

[0035] 2. In clinical trials, this invention, using lifestyle intervention as a control, demonstrated the synergistic effect of traditional Chinese medicine (TCM) and lifestyle intervention. In practical applications, TCM treatment can be combined with dietary and exercise guidance to help patients establish healthy eating and exercise habits, achieving an organic unity of "treating existing diseases" and "preventing diseases."

[0036] 3. Compared to long-term use of Western medicines (such as statins which require long-term use and regular liver function monitoring), this invention uses traditional Chinese medicinal herbs as raw materials, which are widely available, low in cost, highly safe, and do not require frequent monitoring. Based on one dose of decoction per day, the cost of medicinal materials is controllable. If developed into modern dosage forms such as granules or capsules, packaging, transportation, and storage costs can be further reduced. The estimated annual treatment cost per patient is far lower than imported liver-protecting and lipid-lowering drugs, demonstrating significant economic advantages.

[0037] 4. The traditional Chinese medicine composition of this invention can be prepared into various dosage forms as needed, suitable for different scenarios and consumer groups. The raw materials used include Angelica sinensis, Atractylodes macrocephala, Paeonia lactiflora, Paeonia veitchii, Poria cocos, Alisma plantago-aquatica, Salvia miltiorrhiza, Curcuma zedoaria, Crataegus pinnatifida, Nelumbo nucifera leaf, Citrus reticulata peel, and Glycyrrhiza uralensis, all of which are commonly used bulk traditional Chinese medicinal materials. Promotion and application will drive the standardized planting, harvesting, processing, and distribution of these medicinal materials, promoting the development of traditional Chinese medicine agriculture and the rural economy. Attached Figure Description

[0038] Figure 1 A heatmap of clustering for secondary pathway functional annotations (horizontal axis represents group information, vertical axis represents functional annotation information, and the clustering tree on the left side of the figure is the functional clustering tree).

[0039] Figure 2 A heatmap of clustering for functional annotation of three-level pathways (horizontal axis represents group information, vertical axis represents functional annotation information, and the clustering tree on the left side of the figure is the functional clustering tree). Detailed Implementation

[0040] To enable those skilled in the art to better understand the present invention, the technical solution of the present invention will be described in further detail below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort should fall within the scope of protection of the present invention.

[0041] It should be noted that, unless otherwise specified, the embodiments and features described in the present invention can be combined with each other. The present invention will now be described in detail with reference to the embodiments.

[0042] Example 1: Preparation of Liver-Regulating and Turbidity-Clearing Decoction

[0043] A traditional Chinese medicine composition for treating fatty liver disease associated with metabolic dysfunction (based on daily dose) is composed of the following raw materials in parts by weight: Angelica sinensis 10g, Atractylodes macrocephala 15g, Paeonia lactiflora 15g, Paeonia veitchii 15g, Poria cocos 20g, Alisma plantago-aquatica 15g, Salvia miltiorrhiza 20g, Curcuma zedoaria 9g, Crataegus pinnatifida 15g, Nelumbo nucifera leaf 10g, Citrus reticulata peel 10g, and Glycyrrhiza uralensis 6g.

[0044] Preparation method of Tiaogan Huazhuo Decoction, a traditional Chinese medicine composition for treating fatty liver disease related to metabolic dysfunction:

[0045] (1) Weigh each of the above-mentioned raw materials after removing impurities, and set aside for later use;

[0046] (2) Mix the weighed raw materials, place them in a decoction container, add water (about 1360 ml) equal to 8 times the total weight of the medicinal materials, and soak for 40 minutes;

[0047] (3) Heat to a boil, then simmer for 40 minutes.

[0048] (4) Filter the solution through a 100-mesh sieve and collect the first filtrate;

[0049] (5) Add water (about 1020 ml) equal to 6 times the total weight of the medicinal materials to the dregs, heat to boiling and then keep simmering for 30 minutes;

[0050] (6) Filter and combine the two filtrates to obtain the Liver-Regulating and Turbidity-Clearing Decoction, with a volume of about 500 ml.

[0051] Usage: Take one dose daily, twice a day, morning and evening, while warm.

[0052] Example 2: Preparation of Liver-Regulating and Turbidity-Clearing Decoction

[0053] A traditional Chinese medicine composition for treating fatty liver disease associated with metabolic dysfunction (based on daily dose) comprises the following raw materials in parts by weight: Angelica sinensis 15g, Atractylodes macrocephala 10g, Paeonia lactiflora 20g, Paeonia veitchii 10g, Poria cocos 30g, Alisma plantago-aquatica 10g, Salvia miltiorrhiza 30g, Curcuma zedoaria 5g, Crataegus pinnatifida 10g, Nelumbo nucifera leaf 5g, Citrus reticulata peel 5g, and Glycyrrhiza uralensis 3g.

[0054] Preparation method of Tiaogan Huazhuo Decoction, a traditional Chinese medicine composition for treating fatty liver disease related to metabolic dysfunction:

[0055] (1) Weigh each of the above-mentioned raw materials after removing impurities, and set aside for later use;

[0056] (2) Mix the weighed raw materials, place them in a decoction container, add water equal to 10 times the total weight of the medicinal materials, and soak for 30 minutes;

[0057] (3) Heat to a boil, then simmer for 30 minutes.

[0058] (4) Filter the solution through a 100-mesh sieve and collect the first filtrate;

[0059] (5) Add water to the dregs, which is 6 times the total weight of the herbs, and heat to boiling. Then keep it simmering for 20 minutes.

[0060] (6) Filter and combine the two filtrates to obtain the Liver-Regulating and Turbidity-Clearing Decoction, with a volume of about 400 ml.

[0061] Usage: Take one dose daily, twice a day, morning and evening, while warm.

[0062] Example 3: Preparation of Liver-Regulating and Turbidity-Clearing Decoction

[0063] A traditional Chinese medicine composition for treating fatty liver disease associated with metabolic dysfunction (based on daily dose) is composed of the following raw materials in parts by weight: Angelica sinensis 5g, Atractylodes macrocephala 20g, Paeonia lactiflora 10g, Paeonia veitchii 20g, Poria cocos 15g, Alisma plantago-aquatica 20g, Salvia miltiorrhiza 15g, Curcuma zedoaria 12g, Crataegus pinnatifida 20g, Nelumbo nucifera leaf 15g, Citrus reticulata peel 15g, and Glycyrrhiza uralensis 10g.

[0064] Preparation method of Tiaogan Huazhuo Decoction, a traditional Chinese medicine composition for treating fatty liver disease related to metabolic dysfunction:

[0065] (1) Weigh each of the above-mentioned raw materials after removing impurities, and set aside for later use;

[0066] (2) Mix the weighed raw materials, place them in a decoction container, add water equal to 12 times the total weight of the medicinal materials, and soak for 60 minutes;

[0067] (3) Heat to a boil, then simmer for 60 minutes.

[0068] (4) Filter the solution through a 100-mesh sieve and collect the first filtrate;

[0069] (5) Add water equal to 6 times the total weight of the medicinal materials to the dregs, heat to boiling and then keep simmering for 40 minutes;

[0070] (6) Filter and combine the two filtrates to obtain the Liver-Regulating and Turbidity-Clearing Decoction, with a volume of about 600 ml.

[0071] Usage: Take one dose daily, twice a day, morning and evening, while warm.

[0072] Example 4: Preparation of Liver-Regulating and Turbidity-Clearing Granules

[0073] The only difference between this embodiment and Example 1 is the preparation method. The preparation method of this embodiment includes the following steps:

[0074] (1) Weigh each ingredient according to the weight, grind them into coarse powder (pass through a 10-mesh sieve), and mix them evenly;

[0075] (2) Add 10 times the amount of water to the mixed coarse powder, soak for 1 hour, and decoct twice: the first decoction is 1.5 hours, and the second decoction is 1 hour with 8 times the amount of water. Combine the decoctions.

[0076] (3) Filter the combined decoction and concentrate it under reduced pressure (temperature not exceeding 70 degrees Celsius, vacuum degree -0.08 MPa) to a thick paste with a relative density of 1.10 to 1.15 (measured at 60 degrees Celsius);

[0077] (4) Mix the thick paste with an appropriate amount of excipients (such as dextrin, soluble starch, the ratio of thick paste to excipients is 1:1 to 1:2) to make a soft paste;

[0078] (5) Granulate by passing through a 14-mesh sieve and dry at 60 degrees Celsius until the moisture content does not exceed 5%;

[0079] (6) After passing through a 12-mesh sieve to form whole grains, the Liver-Regulating and Turbidity-Clearing Granules are obtained. Each bag contains 8.5 grams of raw medicinal material (i.e., one-twentieth of the daily dose). Take 2 bags daily (1 bag in the morning and 1 bag in the evening).

[0080] Modification Notes: The excipients can be one or more of dextrin, lactose, microcrystalline cellulose, and mannitol; granulation can be carried out by one-step fluidized bed granulation or wet granulation followed by granulation.

[0081] Example 5: Preparation of Liver-Regulating and Turbidity-Clearing Capsules

[0082] The only difference between this embodiment and Example 1 is the preparation method. The preparation method of this embodiment includes the following steps:

[0083] Preparation method:

[0084] (1) Weigh each ingredient according to the weight, grind them into fine powder (pass through an 80-mesh sieve), and mix them evenly;

[0085] (2) The mixed fine powder is granulated by dry method; or the dry extract powder is obtained by decoction and concentration followed by spray drying as in Example 2;

[0086] (3) Mix the granules or dry extract powder with a lubricant (such as magnesium stearate, in an amount of 0.5% to 1% of the total weight);

[0087] (4) Filled into gelatin capsules or hydroxypropyl methylcellulose capsules, each capsule containing 0.3 to 0.5 grams, equivalent to 1.5 to 2.5 grams of raw drug;

[0088] (5) Take 4 to 6 pills daily, divided into 2 to 3 doses.

[0089] Modification instructions: The extract can be used for direct filling, or a diluent (such as starch or microcrystalline cellulose) can be added to adjust the filling volume.

[0090] Example 6: Clinical efficacy of Tiaogan Huazhuo Decoction in treating fatty liver disease related to metabolic dysfunction

[0091] This embodiment demonstrates the therapeutic effect of the traditional Chinese medicine composition of the present invention on patients with metabolic dysfunction-associated fatty liver disease (MASLD) (diagnosed as phlegm-dampness obstruction syndrome in traditional Chinese medicine).

[0092] 1. Research Subjects

[0093] Sixty patients who met the diagnostic criteria for MASLD were selected and randomly divided into a TGHZ group and a control group, with 30 patients in each group.

[0094] 2. Treatment methods

[0095] TGHZ group: Based on the dissemination of health science knowledge and dietary intervention, the patient was given Tiaogan Huazhuo Decoction combined with exercise therapy. That is, on the basis of dietary guidance and exercise, with no less than 150 minutes of moderate-intensity aerobic exercise per week, Tiaogan Huazhuo Decoction prepared in Example 1 was added, one dose per day, divided into two oral doses, for 12 consecutive weeks (one treatment cycle).

[0096] Control group: In addition to receiving health education and dietary interventions, they only received the same exercise therapy interventions.

[0097] After one treatment cycle, the basic demographic characteristics, biochemical indicators, gut microbiota, short-chain fatty acids, and functional predictions of patients in the TGHZ group and the control group were detected and analyzed.

[0098] Efficacy evaluation criteria: The efficacy evaluation criteria were based on the 2002 edition of the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines" and were calculated using the nimodipine method.

[0099] Effective rate = [(Number of clinically cured patients + Number of patients with significant effects + Number of patients with effective results) ÷ Total number of patients] × 100%.

[0100] Clinical cure: Major symptoms and signs disappear or basically disappear, and the efficacy index is ≥95%;

[0101] Significant improvement: Major symptoms and signs show marked improvement, with an efficacy index of 70% ≤ efficacy index < 95%;

[0102] Effective: Major symptoms and signs show significant improvement; efficacy rate ≤ 30% < efficacy index < 70%;

[0103] Ineffective: No significant improvement or even worsening of main symptoms and signs, with an efficacy index of <30%.

[0104] 3. Treatment Results

[0105] 3.1 Indicators of BMI, waist circumference, hip circumference, and waist-to-hip ratio

[0106] Table 1 shows that before treatment, there were no statistically significant differences in BMI, waist circumference, hip circumference, and waist-to-hip ratio between the two groups (P > 0.05), indicating comparability. Intergroup comparisons also showed no statistically significant differences in BMI, waist circumference, hip circumference, and waist-to-hip ratio between the two groups (P > 0.05). Intragroup comparisons showed statistically significant improvements in BMI, waist circumference, hip circumference, and waist-to-hip ratio in the treatment group, while statistically significant improvements were observed in the control group. The mean and standard deviation of BMI, waist circumference, hip circumference, and waist-to-hip ratio before and after treatment indicated a greater decrease in these parameters in the treatment group, suggesting that the Tiaogan Huazhuo Decoction has a positive regulatory effect on weight loss.

[0107] Table 1 Comparison of BMI, waist circumference, hip circumference, and waist-to-hip ratio between the two groups before and after treatment.

[0108]

[0109] Note: Compared with before treatment, *P<0.05, **P<0.01, ***P<0.001.

[0110] 3.2 Comparison of Liver Function Indicators

[0111] Table 2 shows that, within-group comparisons revealed a statistically significant decrease in ALT and AST levels in the treatment group compared to pre-treatment levels (P < 0.05). However, between-group comparisons indicated no statistically significant differences in ALT, AST, alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) levels between the treatment and control groups (P > 0.05). Comparison of the mean and median ALP and GGT levels after treatment revealed that the mean and median ALP and GGT levels in the treatment group were slightly lower than those in the control group. Statistical analysis of abnormal ALT levels showed a significant improvement in the treatment group's ALT levels, although the difference was not statistically significant, suggesting that the Tiaogan Huazhuo Decoction has a tendency to protect the liver and lower enzyme levels.

[0112] Liver enzymes are important indicators of liver damage. Studies have shown that patients with metastatic fatty liver disease (MASLD) are prone to elevated ALT, AST, and GGT levels. Elevated ALT is closely associated with the progression of metabolic-related fatty liver disease to NASH and even liver fibrosis, while AST and the ALT / AST ratio are related to the severity of fatty liver. Furthermore, ALP not only participates in the process of lipid accumulation in adipocytes, but its elevated levels are also associated with various risk factors for MASLD, such as insulin resistance and dyslipidemia.

[0113] White peony root, the principal ingredient in Tiaogan Huazhuo Decoction, aligns with the nature of the liver. It is bitter and slightly cold in nature, possessing the effects of nourishing yin and softening the liver, astringing yin and relieving pain. Fu Qingzhu's *Gynecology* states, "For diseases affecting the liver, white peony root is especially indispensable." Total glycosides of white peony root are important components contributing to its hepatoprotective effects. Modern pharmacological studies suggest that total glycosides of white peony root can regulate ALT and AST levels in a rat model of chemically induced liver injury with liver yin deficiency syndrome, improve hepatocyte energy metabolism, alleviate liver damage, and slow the progression of liver fibrosis.

[0114] Table 2 Comparison of liver function indicators between the two groups before and after treatment.

[0115]

[0116] Note: *P<0.05 compared with pre-treatment levels; TBIL: total bilirubin, DBIL: direct bilirubin, ALB: albumin, GLOB: globulin.

[0117] 3.3 Comparison of blood lipid indicators

[0118] Table 3 shows that after 3 months of treatment, there was a statistically significant difference between the treatment group and the control group (P < 0.05), indicating that the treatment group was significantly more effective than the control group in improving total cholesterol (TC) and triglyceride (TG) levels, while the advantage in improving high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) was not very obvious. However, within-group comparison of LDL-C, the LDL-C level in the treatment group decreased significantly (P < 0.05). Although there were negative results, this is related to the short intervention period and the fact that most subjects' HDL-C and LDL-C levels were still within the normal reference range at the time of enrollment. Nevertheless, the results still suggest that Tiaogan Huazhuo Decoction has a positive regulatory effect on lipid indicators of MASLD.

[0119] In patients with MASLD, dyslipidemia is often accompanied by elevated TG and LDL-C levels and decreased HDL-C levels. This dyslipidemia is also associated with hepatocellular damage, and the decrease in TC, TG, and LDL-C is positively correlated with the normalization rate of ALT, AST, and GGT. Poria cocos, an auxiliary herb in the Liver-Regulating and Turbidity-Eliminating Decoction, is sweet and bland in taste and neutral in nature, possessing diuretic and dampness-eliminating effects. The *Medicinal Herbs and Their Applications* states, "Poria cocos, bland in taste, can clear the orifices; sweet in taste, it assists yang; it is a holy medicine for eliminating dampness." Modern pharmacological studies suggest that the active ingredient in Poria cocos, Poria cocos polysaccharide, can significantly reduce ApoE by improving the abnormal expression of cholesterol reverse transport proteins such as cholesterol ester transporters and phospholipid transporters. - / -The levels of TG, TC, and LDL-C in mice were measured, and liver lipid metabolism was regulated. Hawthorn, a medicinal herb, can aid digestion, reduce food stagnation, lower TC, TG, and LDL-C levels, and raise HDL-C levels. Furthermore, the combined use of its active ingredients—total organic acids from hawthorn fruit and total flavonoids from hawthorn leaves—also has a weight-loss effect.

[0120] Table 3 Comparison of blood lipid levels before and after treatment in the two groups

[0121]

[0122] Note: Compared with before treatment, *P<0.05, **P<0.01; compared with the control group, △P<0.05.

[0123] 3.4 Comparison of liver stiffness values ​​and non-invasive serological scoring models

[0124] As shown in Tables 4 and 5, after 3 months of treatment, there were no statistically significant differences in FIB-4 index, APRI index, and liver stiffness between the treatment group and the control group (P > 0.05). However, intra-group comparisons of FIB-4 index, APRI index, and liver stiffness before and after treatment revealed improvements in FIB-4 index and liver stiffness in the treatment group (P > 0.05). Although the inter-group comparisons showed no statistically significant differences, the intra-group comparisons indirectly suggest that the Tiaogan Huazhuo Decoction may alleviate the progression of liver fibrosis to some extent, and this therapeutic advantage may be validated by extending the treatment course.

[0125] In the course of MASLD, 10%-25% of patients often develop MASH, which further progresses to liver fibrosis and even hepatocellular carcinoma. Therefore, early intervention is crucial to effectively halt the progression of metabolic-related fatty liver disease. International cohort studies have confirmed that the FIB-4 and APRI indices have a certain sensitivity in diagnosing MASLD-related liver fibrosis and can be used as screening tools to stratify liver-related outcomes such as liver-related death, decompensation, and hepatocellular carcinoma.

[0126] Table 4 Comparison of FIB-4 and APRI indices before and after treatment in the two groups

[0127]

[0128] Note: *P<0.05 compared to before treatment.

[0129] Table 5 Comparison of liver stiffness values ​​between the two groups before and after treatment.

[0130]

[0131] Note: *P<0.05 compared to before treatment.

[0132] 3.5 Comparison of uric acid (UA), fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), and high-sensitivity C-reactive protein (hsCRP)

[0133] As shown in Tables 6, 7, and 8, after 3 months of treatment, there were no statistically significant differences in UA, FPG, HbA1c, and hsCRP levels between the treatment group and the control group, both between and within the groups (P > 0.05).

[0134] Table 6 Comparison of UA between the two groups before and after treatment.

[0135]

[0136] Table 7 Comparison of FPG and HbA1c levels between the two groups before and after treatment.

[0137]

[0138] Table 8 Comparison of hsCRP levels before and after treatment in the two groups

[0139]

[0140] 3.5 Overall Clinical Efficacy

[0141] As shown in Table 9, after 3 months of treatment, the overall clinical efficacy of the treatment group was superior to that of the control group, with rates of 76.67% and 46.67%, respectively. The difference was statistically significant (P=0.018) according to the chi-square test. Compared with the control group, the treatment group had significantly more cases with marked or effective results and significantly fewer cases with no effect. The significant difference in TCM symptom scores between the two groups after treatment suggests that the Tiaogan Huazhuo Decoction accurately controls the changes in TCM symptoms of MASLD, effectively alleviating symptoms such as hypochondriac distension, fatigue, bitter taste, and dry mouth associated with MASLD due to liver stagnation and spleen deficiency, phlegm obstruction, and phlegm-blood stasis. This demonstrates that the combination of Tiaogan Huazhuo Decoction and exercise therapy is significantly more effective than exercise therapy alone in alleviating TCM symptoms and improving clinical efficacy, and can significantly improve patients' quality of life. Furthermore, no adverse drug reactions occurred in the 30 patients in the treatment group during the treatment process, and no significant abnormalities were observed in safety indicators.

[0142] Table 9 Comparison of comprehensive clinical efficacy between the two groups before and after treatment.

[0143]

[0144] In summary, the Liver-Clearing and Turbidity-Reducing Decoction prepared from a traditional Chinese medicine composition for treating metabolic dysfunction-related fatty liver disease, combined with lifestyle intervention, provided by this invention, can significantly improve metabolic indicators, liver function, and blood lipid levels in patients with MASLD. The synergistic improvement effect of the above-mentioned multi-dimensional and multi-indicator fully demonstrates that this invention has a comprehensive regulatory effect on the core pathological link of metabolic dysfunction-related fatty liver disease—metabolic disorder—and its efficacy is superior to simple lifestyle intervention.

[0145] Example 7: Effects of a Traditional Chinese Medicine Composition for Regulating Liver Function and Eliminating Turbidity on Intestinal Flora and Short-Chain Fatty Acids in Patients with Fatty Liver Disease Related to Metabolic Dysfunction

[0146] In this embodiment, 25 patients were randomly selected from the treatment group and the control group. Fecal samples were collected from the patients before treatment and 3 months after treatment to complete the 16S rDNA amplicon sequencing of the gut microbiota before and after treatment. Tax4Fun was used to predict and analyze the function of the gut microbiota. By comparing with the KEGG database, functional annotation information was obtained. The top 35 functions in terms of abundance and their distribution in each group of samples were plotted as a clustering heatmap.

[0147] The results indicated that, within the secondary pathways, the treatment group showed higher relative abundance in the secondary pathways of lipid metabolism, cell senescence and death, carbohydrate metabolism, metabolic responses, biosynthesis of other secondary metabolites, and endocrine and metabolic diseases after treatment. The control group showed higher relative abundance in the secondary pathways of transport and catabolism, terpene and polyketide metabolism, cofactor and vitamin metabolism, and glycan biosynthesis and metabolism after treatment (see...). Figure 1 In the three-level pathway, the treatment group showed higher relative abundance in alanine, aspartate, and glutamate metabolism, starch and sucrose metabolism, and gluconeogenesis / glycolysis after treatment. The control group, after treatment, showed higher relative abundance in chromosomes and related proteins, exosomes, cysteine ​​and methionine metabolism, alanine, aspartate, and glutamate metabolism, and the prokaryotic defense system (see...). Figure 2 The above results suggest that Tiaogan Huazhuo Decoction may affect gut microbiota function to some extent by regulating metabolism.

[0148] Furthermore, in this embodiment, 20 patients were randomly selected from the treatment group and 20 patients from the control group. Fecal samples were collected from the patients before treatment and 3 months after treatment to complete the detection of short-chain fatty acids before and after treatment.

[0149] Table 10 Comparison of short-chain fatty acid levels in each group (µg / g)

[0150]

[0151] Table 10 shows that the levels of acetic acid, propionic acid, and butyric acid in the treatment group were all significantly higher than those in the control group. The intergroup comparisons indicated that the differences in acetic acid and butyric acid levels between the treatment and control groups were statistically significant; while the propionic acid level in the control group was significantly higher than before treatment, with a statistically significant difference. Although there was no statistically significant difference in propionic acid levels before and after treatment in the treatment group, the mean and standard deviation of propionic acid increased after treatment, which may suggest that the Tiaogan Huazhuo Decoction has a potential benefit in regulating propionic acid levels.

[0152] In summary, the traditional Chinese medicine composition for regulating liver function and clearing turbidity can improve lipid metabolism disorders, increase the content of acetic acid and butyric acid, and show a trend of increasing propionic acid content.

[0153] The Liver-Regulating and Turbidifying Decoction provided by this invention is based on the theory of Qi transformation and combined with the pathogenesis of MASLD. It is established with the treatment principle of strengthening the spleen and regulating the liver, eliminating dampness and turbidity, and promoting blood circulation and softening hardness. It is derived from Dang Gui Shao Yao San and Ze Xie Tang and is composed of Angelica sinensis, Atractylodes macrocephala, Paeonia lactiflora, Paeonia veitchii, Poria cocos, Alisma plantago-aquatica, Salvia miltiorrhiza, Curcuma zedoaria, Crataegus pinnatifida, Nelumbo nucifera, Citrus reticulata, Glycyrrhiza uralensis, etc. In the formula, Atractylodes macrocephala and Paeonia lactiflora are the principal herbs. Atractylodes macrocephala is sweet and bitter in taste and warm in nature. It can dry dampness and strengthen the spleen, and also soothe the spleen and generate fluids. When the spleen is healthy, dampness and phlegm will be eliminated and the Qi mechanism will flow smoothly throughout the body. Li Dongyuan said that it can "remove dampness in all meridians and regulate the spleen and stomach". At the same time, Atractylodes macrocephala is aromatic and warm, which can also help the liver Qi to flow smoothly, thus regulating the liver and spleen. Peony root has a sour, bitter, and sweet taste, and enters the liver and spleen meridians. It benefits spleen yin and nourishes liver yin. The Compendium of Materia Medica records that "white peony benefits the spleen and can drain wood from the earth; red peony disperses evil and can move stagnation in the blood." White peony root astringes while red peony root disperses, nourishing and activating blood at the same time, benefiting yin and moistening the liver and spleen. When used together with peony root, Atractylodes macrocephala has a balanced opening and closing effect, strengthening the spleen and regulating the liver, ensuring a source for the generation of qi and blood.

[0154] This specific embodiment is merely an explanation of the present invention and is not intended to limit the invention. After reading this specification, those skilled in the art can make modifications to this embodiment without contributing any inventive step, but such modifications are protected by patent law as long as they are within the scope of the claims of the present invention.

Claims

1. A traditional Chinese medicine composition for treating fatty liver disease related to metabolic dysfunction, characterized in that, The traditional Chinese medicine composition consists of the following raw medicinal materials in parts by weight: Angelica sinensis 5-15 parts, Atractylodes macrocephala 10-20 parts, Paeonia lactiflora 10-20 parts, Paeonia veitchii 10-20 parts, Poria cocos 15-30 parts, Alisma plantago-aquatica 10-20 parts, Salvia miltiorrhiza 15-30 parts, Curcuma zedoaria 5-12 parts, Crataegus pinnatifida 10-20 parts, Nelumbo nucifera leaf 5-15 parts, Citrus reticulata peel 5-15 parts, and Glycyrrhiza uralensis 3-10 parts.

2. The traditional Chinese medicine composition for treating fatty liver disease related to metabolic dysfunction according to claim 1, characterized in that, The traditional Chinese medicine composition consists of the following raw medicinal materials in parts by weight: Angelica sinensis 10 parts, Atractylodes macrocephala 15 parts, Paeonia lactiflora 15 parts, Paeonia veitchii 15 parts, Poria cocos 20 parts, Alisma plantago-aquatica 15 parts, Salvia miltiorrhiza 20 parts, Curcuma zedoaria 9 parts, Crataegus pinnatifida 15 parts, Nelumbo nucifera leaf 10 parts, Citrus reticulata peel 10 parts, and Glycyrrhiza uralensis 6 parts.

3. A method for preparing a drug for treating fatty liver disease related to metabolic dysfunction using the traditional Chinese medicine composition according to claim 1 or 2, characterized in that, include: The raw materials in the Chinese herbal composition are weighed according to their weight proportions, and after being pulverized and / or decocted, any acceptable pharmaceutical preparation is prepared with or without medically acceptable excipients.

4. The method according to claim 3, characterized in that, The particle size of the pulverized material is 10-80 mesh.

5. The method according to claim 3, characterized in that, The ingredients need to be soaked for 30-60 minutes before frying.

6. The method according to claim 3, characterized in that, The decoction process includes: adding 6 to 12 times the total weight of the raw materials to water and decocting for 30 to 90 minutes; after filtration, adding 4 to 8 times the total weight of the raw materials to water to decoct for 20 to 60 minutes.

7. The method according to claim 3, characterized in that, The dosage form of the drug is decoction, powder, granules, tablets or capsules.

8. The method according to claim 3, characterized in that, The excipients are one or more of dextrin, soluble starch, lactose, microcrystalline cellulose, mannitol, and magnesium stearate.

9. A medicament for treating metabolic dysfunction-related fatty liver disease prepared by the method according to any one of claims 4-8.

10. The use of the medicament according to claim 9 in the preparation of a medicament for treating metabolic dysfunction-related fatty liver disease.

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